Summary
Plasma and ascitic fluid concentrations of ofloxacin were determined in 12 cirrhotic patients after a single dose and repeated 200 mg oral doses. The single dose kinetics were compared to those obtained in 12 healthy volunteers.
Mean plasma elimination half-life was 11.6 h in cirrhotics and 7.0 h in controls. Mean total clearance was 2.3 times lower in patients than in controls, due to a significant decrease of renal clearance of the drug, unrelated to creatinine clearance. Mean apparent volume of distribution was 1.2 l/kg in patients and 1.8 l/kg in controls. Estimated by the ratio of AUC in peritoneal fluid and plasma, ascitic fluid penetration was 80% after the first oral dose. Ascitic fluid concentrations equaled corresponding plasma concentrations after 10 h, without pronounced accumulation of ofloxacin in ascites.
We may conclude that, in cirrhotic patients with normal serum creatinine, a significant impairment of renal tubular handling of ofloxacin could be observed and led to a delayed elimination half-life of the drug.
Because of its broad sprectrum of activity, low side-effect profile, and large ascitic fluid penetration after oral administration, ofloxacin appears to be a new therapeutic approach of severe infections in cirrhotic patients, in particular spontaneous bacterial peritonitis.
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References
Monk JP, Campoli-Richards DM (1987) Ofloxacin: A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 33: 346–391
Lode H, Hoffken G, Olschewski P, Sievers B, Kirch A, Borner K, Koeppe P (1987) Pharmacokinetics of ofloxacin after parenteral and oral administration. Antimicrob Agents Chemother 31: 1338–1342
Neu HC (1987) Clinical use of the quinolones. Lancet 2: 1319–1322
Smith CR (1987) The adverse effects of fluoroquinolones. J Antimicrob Chemother 19: 709–712
Cabrera J, Arroyo V, Ballesta AM, Rimola A, Gual J, Elena M, Rodes J (1982) Aminoglycoside nephrotoxicity in cirrhosis. Value of urinary β2-mibroglobulin to discriminate functional renal failure from acute tubular damage. Gastroenterology 82: 97–105
Felisart J, Rimola A, Arroyo V, Perez-Ayuso RM, Quintero E, Gines P, Rodes J (1985) Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections. Hepathology 5: 457–462
Montay G, Tassel JP (1985) Improved high-performance liquid chromatographic determination of pefloxacin and its metabolite norfloxacin in human plasma and tissue. J Chromatogr 339: 214–218
Gomeni R (1983) An interactive program for individual and population parameter estimation. In: Von Bommel NG, Ball MJ, Wigertz NO (eds) Medinfo 83. North Holland, Amsterdam
Chiou WL (1978) Comparison of plasma creatinine levels in patients determined by high-pressure liquid chromatographic determination of endogenous true creatinine in plasma, serum, urine. J Pharm Sci 67: 182–187
Flor S, Beals B, Tack K, Weintraub H (1987) Pharmacokinetics of ofloxacin in healthy geriatric subjects after single oral dose and during multiple oral dose administration. 27th ICAAC New York, USA, 1261 (abstract, see footnote)
Papadakis MA, Arieff AI (1987) Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study. Am J Med 82: 945–952
Lewis GP, Jusko WJ (1975) Pharmacokinetics of amplicillin in cirrhosis. Clin Pharmacol Ther 18: 475–484
Villeneuve JP, Fortunet-Fouin H, Arsène D (1983) Cimetidine kinetics and dynamics in patients with severe liver disease. Hepatology 3: 923–927
Blaschke TF (1977) Protein binding and kinetics of drugs in liver diseases. Clin Pharmacokinet 2: 32–44
Secor JW, Schenker S (1987) Drug metabolism in patients with liver disease. Adv Intern Med 32: 379–406
Cardey J, Silvain C, Bouquet S, Breux JP, Becq-Giraudon B, Fourtillan JP, Beauchant M (1987) Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis. Eur J Clin Pharmacol 33: 469–472
Silvain C, Breux JP, Rochard E, Bouquet S, Becq-Giraudon B, Beauchant M (1987) Decreased erythrocyte penetration of pefloxacin in cirrhotic patients. J Antimicrob Chemother 20: 290–292
Barza M, Cuchural B (1985) General principles of antibiotic tissue penetration. J Antimicrob Chemother 15 [Suppl A]: 59–75
Gerding DN, Kromhout JP, Sullivan JJ, Hall WH (1976) Antibiotic penetrance of ascitic fluid in dogs. Antimicrob Agents Chemother 10: 850–855
Bint AJ (1987) Pharmacokinetics of antibiotics in peritoneal dialysis. J Antimicrob Chemother 20: 626–628
Gerding DN, Hall WH, Schierl EA (1977) Antibiotic concentrations in ascitic fluid of patients with ascites and bacterial peritonitis. Ann Intern Med 86: 708–713
Krediet RT, Zuyderhoudt FMJ, Boeschoten EW, Arisz L (1987) Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. Eur J Clin Invest 17: 43–52
Smithivas T, Hyams PJ, Matalon R, Simberkoff MS, Rahal JJ (1971) The use of gentamicin in peritoneal dialysis. I. Pharmacologic results. J Infect Dis 124 [Suppl]: S77-S83
Hoefs JC, Canawati HN, Sapico FL, Hopkins RR, Weiner J, Montgomerie JZ (1982) Spontaneous bacterial peritonitis. Hepatology 2: 399–407
Janknegt R (1986) Fluorinated quinolones. A review of their mode of action, antimicrobial activity, pharmacokinetics and clinical efficacity. Pharm Weekbl [Sci] 8: 1–21
Sanders CC, Sanders WE, Goering RV, Werner V (1984) Selection of multiple antibiotic resistance by quinolones betalactams and aminoglycosides with special reference to cross resistance between unrelated drug classes. Antimicrob Agents Chemother 26: 797–801
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Silvain, C., Bouquet, S., Breux, J.P. et al. Oral pharmacokinetics and ascitic fluid penetration of ofloxacin in cirrhosis. Eur J Clin Pharmacol 37, 261–265 (1989). https://doi.org/10.1007/BF00679781
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DOI: https://doi.org/10.1007/BF00679781